Potential Protective Mechanism in the Cardiac Microvascular InjuryNovelty and Significance [Heart]

This study was performed to determine the detailed role of TRPV1 in cardiac microvascular endothelial cells (CMECs) in T2DM. T2DM mice were established by multiple injections of low-dose streptozotocin and high-fat feeding. CMECs were cultured separately in mediums of normal glucose, high glucose (HG), high fatty acid (HF), and HG plus HF (HG-HF). HG-HF inhibited TRPV1 expression in CMECs, reducing cellular Ca2+ content ([Ca2+]i). T2DM impaired cardiac function, disturbed glucose uptake, and damaged microvascular barrier, which were further aggravated by TRPV1−/−. Exposure to HG-HF, particularly in TRPV1−/− CMECs, led to a higher level of apoptosis and a lower level of nitric oxide production in viable CMECs. HG-HF markedly enhanced generation of reactive oxygen species and nitrotyrosine, especially in the absence of TRPV1. H2O2 administration reduced TRPV1 expression in CMECs. HG-HF significantly depressed expression of PGC-1α (peroxisome proliferator–activated receptor-γ coactivator-1α) and OPA1 (optic atrophy 1) by reducing [Ca2+]i, whereas OPA1 supplementation partly reversed those detrimental effects induced by TRPV1−/−. Furthermore, capsaicin treatment not only attenuated CMECs injury induced by HG-HF but also mitigated cardiac microvascular injury induced by T2DM. Collectively, T2DM leads to cardiac microvascular injury by exacerbating the vicious circle of TRPV1 blockage and reactive oxygen species overload. Long-term capsaicin can protect cardiac mic...
Source: Hypertension - Category: Cardiology Authors: Tags: Animal Models of Human Disease, Cell Signaling/Signal Transduction Original Articles Source Type: research